AMPK synergizes with the combined treatment of 1′-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities
Article first published online: 5 APR 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 7, pages 1198–1208, July 2013
How to Cite
Yaku, K., Matsui-Yuasa, I., Konishi, Y. and Kojima-Yuasa, A. (2013), AMPK synergizes with the combined treatment of 1′-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities. Mol. Nutr. Food Res., 57: 1198–1208. doi: 10.1002/mnfr.201200809
- Issue published online: 1 JUL 2013
- Article first published online: 5 APR 2013
- Manuscript Accepted: 12 FEB 2013
- Manuscript Revised: 24 JAN 2013
- Manuscript Received: 6 DEC 2012
- Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of the Science. Grant Numbers: 21500783, 24500987
- 1’-Acetoxychavicol acetate;
- AMP-activated protein kinase;
- Dietary fiber;
- Phase II enzyme;
- Rat intestine epithelial cells
Phase II enzymes play important roles in detoxifying xenobiotics. We previously reported that both 1’-acetoxychavicol acetate (ACA) and sodium butyrate individually increased phase II enzyme activities. Here, we determined the combined action of ACA and sodium butyrate on phase II enzyme activities in intestinal epithelial cells (IEC 6).
Methods and results
ACA and sodium butyrate synergistically increased phase II enzyme activities. Protein levels of intranuclear transcription factor NF-E2–related factor 2 (Nrf2) were increased by ACA or sodium butyrate treatment, but treatment with both did not produce a synergistic effect. Intranuclear p53 protein levels were increased by ACA but decreased by sodium butyrate alone or combined treatment with ACA and sodium butyrate. In contrast, p53 acetylation was promoted by sodium butyrate and the ACA and sodium butyrate combination. Inhibition of AMPK activity decreased phase II enzyme activities that were upregulated by treatment with ACA plus sodium butyrate or other phytochemicals, including kaempferol, quercetin, and epigallocatechin-3-gallate. Combined treatment with ACA and sodium butyrate increased phosphorylated AMPK levels.
These results suggest that ACA and sodium butyrate synergistically contribute to xenobiotics metabolism. The combined ACA and sodium butyrate treatment synergistically upregulated phase II enzyme activities through AMPK activation and p53 acetylation.